Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in the United States. Acute exacerbations of chronic bronchitis (AECBs), defined as the acute worsening of breathlessness, cough, sputum volume or sputum purulence, are associated with marked acute deteriorations of symptoms, health related quality of life and pulmonary function. Clinical studies in COPD and AECB are sorely needed. We propose to develop a Clinical Skills Development Core to rigorously train junior investigators in the design, conduct and analysis of clinical trials focused on COPD related topics. The core will include a multidisciplinary group of investigators with expertise in clinical study design and conduct, inflammation and host responses, systematic analysis of the literature and the study of economic implications of new technology. Acute infection underlies up to 70% of episodes of AECB, while inflammation is important in the genesis of symptomatic exacerbations. It is likely that infection is an important trigger of airway inflammation in COPD. The 14 and 15 membered macrolides have been demonstrated to exhibit important, anti-inflammatory effects. These agents have assumed a pivotal role in the treatment of diffuse panbronchiolitis and cystic fibrosis, while preliminary positive results have been demonstrated in patients with bronchiectasis and COPD. Pulmonary rehabilitation relieves dyspnea, fatigue and enhances the COPD patient's sense of control although the impact in patients with a recent AECB remains unclear. In this application we propose two research protocols for a Clinical Research Network (CRN) in COPD: 1) a randomized, prospective trial comparing a macrolide antibiotic administered chronically over a nine month period versus usual care in COPD patients with a history of frequent exacerbations; and 2) a randomized, prospective trial comparing a four week comprehensive pulmonary rehabilitation program after discharge for an AECB compared with discharge followed by usual care. In addition, we agree to 1) cooperate with other clinical research centers in the development, design and implementation of network wide protocols; 2) abide by common definitions and methodology to assure completion of protocols; 3) comply with study policies and quality assurance measures; 4) accept awards based on per-patient rates and the number of protocols developed and carried out by the CRN; 5) transmit study data to the Data and Coordinating Center; 6) report all adverse events; and 7) develop and adhere to common plans for the dissemination and publication of results.